Bax deficiency reduces infarct size and improves long-term function after myocardial infarction.

We have previously found that, following myocardial ischemia/reperfusion injury, isolated hearts from bax gene knockout mice [Bax(-/-)] exhibited higher cardioprotection than the wild-type. We here explore the effect of Bax(-/-), following myocardial infarction (MI) in vivo. Homozygotic Bax(-/-) and matched wild-type were studied. Mice underwent surgical ligation of the left anterior descending coronary artery (LAD). The progressive increase in left-ventricular end diastolic diameter, end systolic diameter, in Bax(-/-) was significantly smaller than in Bax(+/+) at 28 d following MI (p < 0.03) as seen by echocardiography. Concomitantly, fractional shortening was higher (35 +/- 4.1% and 27 +/- 2.5%, p < 0.001) and infarct size was smaller in Bax(-/-) compared to the wild-type at 28 days following MI (24 +/- 3.7 % and 37 +/- 3.3%, p < 0.001). Creatine kinase and lactate dehydrogenase release in serum were lower in Bax(-/-) than in Bax(+/+) 24 h following MI. Caspase 3 activity was elevated at 2 h after MI only in the wild-type, but reduced to baseline values at 1 and 28 d post-MI. Bax knockout mice hearts demonstrated reduced infarct size and improved myocardial function following permanent coronary artery occlusion. The Bax gene appears to play a significant role in the post-MI response that should be further investigated.

Effect of adenosine A2A receptor agonist (CGS) on ischemia/reperfusion injury in isolated rat liver.

Ischemia/reperfusion injury during liver transplantation is a major cause of primary nonfunctioning graft for which there is no effective treatment other than retransplantation. Adenosine prevents ischemia-reperfusion-induced hepatic injury via its A2A receptors. The aim of this study was to investigate the role of A2A receptor agonist on apoptotic ischemia/reperfusion-induced hepatic injury in rats. Isolated rat livers within University of Wisconsin solution were randomly divided into four groups: (1) continuous perfusion of Krebs-Henseleit solution through the portal vein for 165 minutes (control); (2) 30-minute perfusion followed by 120 minutes of ischemia and 15 minutes of reperfusion; (3) like group 2, but with the administration of CGS 21680, an A2A receptor agonist, 30 microg/100 ml, for 1 minute before ischemia; (4) like group 3, but with administration of SCH 58261, an A2A receptor antagonist. Serum liver enzyme levels were measured by biochemical analysis, and intrahepatic caspase-3 activity was measured by fluorometric assay; apoptotic cells were identified by morphological criteria, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorometric assay, and immunohistochemistry for caspase-3. Results showed that at 1 minute of reperfusion, there was a statistically significant reduction in liver enzyme levels in the animals pretreated with CGS (p < 0.05). On fluorometric assay, caspase-3 activity was significantly decreased in group 3 compared to group 2 (p < 0.0002). The reduction in postischemic apoptotic hepatic injury in the CGS-treated group was confirmed morphologically, by the significantly fewer apoptotic hepatocyte cells detected (p < 0.05); immunohistochemically, by the significantly weaker activation of caspase-3 compared to the ischemic group (p < 0.05); and by the TUNEL assay (p < 0.05). In conclusion, the administration of A2A receptor agonist before induction of ischemia can attenuate postischemic apoptotic hepatic injury and thereby minimize liver injury. Apoptotic hepatic injury seems to be mediated through caspase-3 activity.

TPEN attenuates hepatic apoptotic ischemia/ reperfusion injury and remote early cardiac dysfunction.

The release of cardioactive substances during hepatic ischemia/reperfusion injury generates toxic free radicals that inflict hepatic and remote cardiac damage. The aim of the study was to determine whether TPEN, a potent iron chelator, ameliorates the apoptotic hepatic and cardiac function injuries. Three groups of isolated rat livers were studied: (1) continuously perfused with Krebs-Henseleit solution; (2) subjected to 120 min of ischemia and 15 min of reperfusion; (3) as in group 2, with TPEN administered prior to ischemia. Isolated hearts were perfused for 65 min with the effluent of the reperfused livers. Results showed that TPEN administration reduced the release of norepinephrine, epinephrine, dopamine, prostaglandin E2 and angiotensin II, decreased intrahepatic caspase-3 activity, and decreased the mean hepatocyte apoptotic index (TUNEL assay) (p = 0.001). Perfusion with post-ischemic hepatic effluent caused a transient 15-min increase in left ventricular contraction and coronary flow (p < 0.05), followed by a decrease in cardiac function at one hour. TPEN reduced the transient elevation in left ventricular contraction p < 0.05), but did not prevent the subsequent decrease in cardiac function. In conclusion, TPEN attenuates post-ischemic apoptotic hepatic injury by modulating caspase-3-like activity and reduces the cardioactive substances released from the liver.

Knotting of a pulmonary artery catheter in the superior vena cava: surgical removal and a word of caution.

A case of postoperative pulmonary artery catheterisation complicated by knotting of the catheter (Swan-Ganz) within the superior vena cava is described. The catheter was cut off at the skin entry site. The remainder, together with the knot, was pulled out through a purse string incision in the superior vena cava.

Recombinant factor VIIa use in cardiac surgery--expanding the arsenal therapy for intractable bleeding?

A 72-year-old patient was admitted for mitral valve replacement because of infective endocarditis. Severe intractable bleeding in the early postoperative period was successfully treated with recombinant activated factor VII (rFVIIa). Thereafter, recovery was uneventful, and the patient was discharged on postoperative day 16. The current clinical aspects and experience of rFVIIa use in cardiac surgery are discussed.

Nausea and vomiting after fast-track cardiac anaesthesia.

BACKGROUND: The aim of this study was to determine the prevalence of postoperative nausea and vomiting (PONV) after fast-track cardiac anaesthesia, risk factors for PONV and its influence on the length of stay in the intensive care unit (ICU). METHODS: A prospective study was performed in the cardiothoracic ICU (CTICU) of a university hospital; 1221 consecutive patients undergoing fast-track anaesthesia (FTCA) in cardiac surgery were enrolled in the study. Severity of PONV was assessed immediately after extubation and then every hour until discharge from the CTICU. Metoclopramide 10 mg i.v. was used as a first-line rescue medication and ondansetron 4 mg i.v. as second-line rescue medication for PONV. RESULTS: Nausea was reported in 240 (19.7%) patients, and vomiting in 53 (4.3%). A total of 269 (22%) patients were treated with metoclopramide and 38 (3.1%) with metoclopramide and ondansetron. The latter was effective in all cases. Risk factors for PONV were age less than 60 yr, female gender and previous history of PONV. Discharge from the CTICU was delayed for a few hours because of PONV in eight patients, all of whom were discharged the same day. CONCLUSIONS: The incidence of PONV is relatively low after FTCA and does not prolong ICU stay. Prophylactic administration of anti-emetic drugs before FTCA is not necessary.